T90/44 (9.3 antigen). A cell surface molecule with a function in human T cell activation

Abstract

T90/44 is a cell surface antigen which is present on human T cells of the helper and cytotoxic subsets and which binds the 9.3 monoclonal antibody (9.3 mAb). It is expressed in the form of 90‐kDa disulfide‐bonded dimers of a 44‐kDa polypeptide and of free 44‐kDa subunits. The function of T90/44 was investigated in a series of T cell function assays. 9.3 mAb was found to inhibit the activation of class II‐restricted cloned T helper cells derived from leprosy patients and reactive with M. leprae antigens. The inhibition was first found at 1–10 ng/ml 9.3 mAb and regularly increased with the antibody concentration. The extent of the inhibition varied among different T cell clones in proportion to the respective different levels of T90/44 expression at their cell surface. The proliferative responses of peripheral blood lymphocytes (PBL) to purified protein derivative of M. tuberculosis (PPD) and tetanus toxoid were enhanced by the 9.3 mAb resulting in up to 20–30‐fold increase of [3H]‐thymidine incorporation. After phytohemagglutinin‐induced activation of PBL, the number of T90/44 molecules per cell expressed at the cell surface rose from day 0 to day 7 by a factor of about 10. High concentrations of 9.3 mAb (5–10 μ/ml) at low cell densities and in the presence of monocytes in culture media supplemented by fetal calf serum were directly mitogenic for resting lymphocytes. The cytolytic effector functions of class I‐restricted cytotoxic T lymphocytes (CTL) were not modulated by 9.3 mAb. The mixed lymphocyte reactions of three class I‐restricted CTL to their specific target cells were found not to be significantly influenced bv 9.3 mAb. In conclusion it is proposed that an antigen‐independent T cell activation pathway can be entered at T90/44.

Presence of HIV-1 Gag-Specific IFN-γ+IL-2+ and CD28+IL-2+ CD4 T Cell Responses Is Associated with Nonprogression in HIV-1 Infection

“…The disruption to the specific CD28 ϩ IL-2 ϩ subset may in turn reflect differences in the state of activation of HIVcompared with CMV-specific cells. CD28 levels and function are up-regulated during T cell activation with polyclonal activators (26,48). Engagement of CD28 with anti-CD28 mAb also augments proliferation of human T cells in the presence of tetanuspulsed costimulation-deficient APC (49).…”

T-cell antigen CD28 mediates adhesion with B cells by interacting with activation antigen B7/BB-1.

“…Many adhesion molecules mediate T-cell-B-cell interactions during an immune response and levels of several, including CD28 and B7/BB-1, increase after activation (1,11,25,32,33,35,36). Increased levels of these molecules may help explain why activated B cells are more effective at stimulating antigen-specific T-cell proliferation than are resting B cells (37)(38)(39)(40).…”

CD28 co‐signaling in the adaptive immune response

“…[10][11][12][13] CD28 was first identified in the 1980s as a co-receptor that enhanced TCR-induced proliferation and promoted the differentiation of naïve CD4 + T cells. 14,15 It encodes a 44 kDa type I transmembrane glycoprotein that homodimerises due to disulphide bonds between cysteines juxta-positioned in the transmembrane region. 16 Cd28 gene has been mapped to human chromosome 2q33 and mouse chromosome 1.…”